Psychological flexibility and fear of cancer recurrence are important variables that influence psychosocial outcomes in individuals diagnosed with a range of different types of cancer. Their role and how they impact on psychological distress and quality of life in men with prostate cancer specifically have not been established.A cross-sectional sample of 144 men with prostate cancer was recruited. Multiple regression and conditional process analysis were used to assess whether psychological flexibility moderates the relationship between fear of recurrence and distress and quality of life.Psychological flexibility significantly predicted psychological distress (β = -0.56, p < 0.0001) and quality of life (β = 0.21, p < 0.0001), appearing a stronger predictor of psychological distress than fear of recurrence (β = 0.25, p < 0.0001). Fear of recurrence was a stronger predictor of quality of life (β = -0.41, p < 0.0001) than psychological flexibility. Psychological flexibility moderated the relationship between fear of recurrence and psychological distress (β = -0.01, p < 0.001). At low and average levels of psychological flexibility, psychological distress mediated the relationship between fear of recurrence and quality of life (β = -0.33 to -0.16, p < 0.05). At high levels of psychological flexibility, distress no longer mediated this relationship (β = 0.01, ns), supporting the role of psychological flexibility as a moderator.These findings suggest that psychological flexibility might be a useful treatment target, through interventions such as Acceptance and Commitment Therapy, to buffer the effects of fear of recurrence and distress and improve psychosocial outcomes in this population.